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Building a Better Quaternary Ammonium Compound (QAC): Branched Tetracationic Antiseptic Amphiphiles
Author(s) -
Forman Megan E.,
Jennings Megan C.,
Wuest William M.,
Minbiole Kevin P. C.
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600176
Subject(s) - antiseptic , disinfectant , cationic polymerization , biofilm , antimicrobial , benzalkonium chloride , ammonium , biocide , toxicity , amphiphile , bacteria , chemistry , antibacterial activity , microbiology and biotechnology , biology , organic chemistry , copolymer , genetics , polymer
Bacteria contaminate surfaces in a wide variety of environments, causing severe problems across a number of industries. In a continuation of our campaign to develop novel antibacterial quaternary ammonium compounds (QACs) as useful antiseptics, we have identified a starting material bearing four tertiary amines, enabling the rapid synthesis of several tris‐ and tetracationic QACs. Herein we report the synthesis and biological activity of a series of 24 multiQACs deemed the “superT” family, and an investigation of the role of cationic charge in antimicrobial and anti‐biofilm activity, as well as toxicity. This class represents the most potent series of QACs reported to date against methicillin‐resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentrations (MICs) and minimum biofilm eradication concentrations (MBECs) as low as 0.25 and 25 μ m , respectively. Based on the significant cell‐surface‐charge differences between bacterial and eukaryotic cells, in certain cases we observed excellent efficacy‐to‐toxicity profiles, exceeding a 100‐fold differential. This work further elucidates the chemical underpinnings of disinfectant efficacy versus toxicity based on cationic charge.